Identification of substituted pyrazolo[1,5-a]quinazolin-5(4H)-one as potent poly(ADP-ribose)polymerase-1 (PARP-1) inhibitors

Synthesis and SAR studies of a novel series of substituted pyrazolo[1,5-a]quinazolin-5(4H)-one derivatives as potent class of PARP-1 inhibitors are reported. A novel series of pyrazolo[1,5-a]quinazolin-5(4H)-one derivatives proved to be a potent class of PARP-1 inhibitors. An extensive SAR around th...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2009-08, Vol.19 (15), p.4196-4200
Main Authors: Orvieto, Federica, Branca, Danila, Giomini, Claudia, Jones, Philip, Koch, Uwe, Ontoria, Jesus M., Palumbi, Maria Cecilia, Rowley, Michael, Toniatti, Carlo, Muraglia, Ester
Format: Article
Language:English
Subjects:
Amides - chemistry
Antineoplastic agents
Biological and medical sciences
Chemistry, Organic - methods
Chemistry, Pharmaceutical - methods
Drug Design
Drug Evaluation, Preclinical
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - pharmacology
General aspects
HeLa Cells
Humans
Inhibitory Concentration 50
Medical sciences
Models, Chemical
Molecular Structure
PARP-1 inhibitor
Pharmacology. Drug treatments
Poly(ADP-ribose) Polymerase Inhibitors
Pyrazole
Pyrazoles - chemical synthesis
Pyrazoles - pharmacology
Quinazolinones - chemical synthesis
Quinazolinones - pharmacology
Structure-Activity Relationship
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Summary:Synthesis and SAR studies of a novel series of substituted pyrazolo[1,5-a]quinazolin-5(4H)-one derivatives as potent class of PARP-1 inhibitors are reported. A novel series of pyrazolo[1,5-a]quinazolin-5(4H)-one derivatives proved to be a potent class of PARP-1 inhibitors. An extensive SAR around the 3-position of pyrazole in the scaffold led to the discovery of amides derivatives as low nanomolar PARP-1 inhibitors.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2009.05.113